DNA polymerase ζ generates tandem mutations in immunoglobulin variable regions

• DOI: 10.1084/jem.20112234
• Publication Date: 2012-05-22T02:51:23Z
• Authors: Huseyin Saribasak; Robert W. Maul; Zheng Cao; William W. Yang; Dominik Schenten; Sven Kracker; Patricia J. Gearhart
• Keywords: Processivity; RNA polymerase III; DNA polymerase II; DNA polymerase mu

Low-fidelity DNA polymerases introduce nucleotide substitutions in immunoglobulin variable regions during somatic hypermutation. Although polymerase (pol) η is the major low-fidelity polymerase, other may also contribute. Existing data are contradictory as to whether pol ζ involved. We reasoned that presence of mask contribution ζ, and therefore we generated mice deficient for heterozygous ζ. The frequency spectra hypermutation was unaltered between Polζ+/− Polη−/− Polζ+/+ clones. However, there a decrease tandem double-base cells compared with cells, suggesting generates mutations. Contiguous mutations consistent biochemical property extend mismatch second mutation. this unique signature implies contributes mutational synthesis vivo. Additionally, on from wild type, Polζ+/−, Polζ−/−, Ung−/−, Msh2−/−, Msh6−/−, Ung−/− Msh2−/− clones suggest function MSH2–MSH6 pathway.